MCID: 3MT016
MIFTS: 45

3-Methylglutaconic Aciduria, Type Iii

Categories: Genetic diseases, Eye diseases, Cardiovascular diseases, Rare diseases, Metabolic diseases, Neuronal diseases

Aliases & Classifications for 3-Methylglutaconic Aciduria, Type Iii

MalaCards integrated aliases for 3-Methylglutaconic Aciduria, Type Iii:

Name: 3-Methylglutaconic Aciduria, Type Iii 53 38 13
3-Methylglutaconic Aciduria Type 3 12 23 24 55 28 14 69
Optic Atrophy 12 72 28 51 41 14 69
Costeff Syndrome 53 12 23 24 55 71
Costeff Optic Atrophy Syndrome 12 23 24 55 71
Mga3 53 12 24 55 71
Optic Atrophy Plus Syndrome 53 23 24 71
Infantile Optic Atrophy with Chorea and Spastic Paraplegia 12 24 55
Autosomal Recessive Optic Atrophy Plus Syndrome 12 55
Opa3-Related 3-Methylglutaconic Aciduria 38 23
Autosomal Recessive Optic Atrophy Type 3 12 55
3-Methylglutaconic Aciduria Type Iii 12 24
Mga, Type Iii 53 24
Mgca3 53 71
Optic Atrophy, Infantile, with Chorea and Spastic Paraplegia 53
3-Alpha-Methylglutaconic Aciduria Type 3 71
Optic Atrophy 3, Autosomal Recessive 53
Autosomal Recessive Optic Atrophy 3 24
Optic Atrophy 3 Autosomal Recessive 71
Iraqi-Jewish 'optic Atrophy Plus' 53
Iraqi-Jewish Optic Atrophy Plus 12
Iraqi Jewish Optic Atrophy Plus 24
3-Methylglutaconic Aciduria 3 71
Optic Atrophies, Hereditary 41
Opa3, Autosomal Recessive 53
Autosomal Recessive Opa3 24
Atrophy of Optic Disc 12
Mga, Type Iii; Mga3 53
Mga Type Iii 71
Opa3 Defect 24

Characteristics:

Orphanet epidemiological data:

55
3-methylglutaconic aciduria type 3
Inheritance: Autosomal recessive; Age of onset: Childhood;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
onset of optic atrophy in infancy or early childhood
neurologic features occur later in childhood
increased prevalence in individuals of jewish-iraqi origin
allelic disorder to autosomal dominant optic atrophy and cataract


HPO:

31
3-methylglutaconic aciduria, type iii:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for 3-Methylglutaconic Aciduria, Type Iii

Genetics Home Reference : 24 Costeff syndrome is a condition characterized by vision loss, movement problems, and intellectual disability. People with Costeff syndrome have degeneration (atrophy) of the optic nerves, which carry information from the eyes to the brain. This optic nerve atrophy often begins in infancy or early childhood and results in vision loss that worsens over time. Some affected individuals have rapid and involuntary eye movements (nystagmus) or eyes that do not look in the same direction (strabismus).

MalaCards based summary : 3-Methylglutaconic Aciduria, Type Iii, also known as 3-methylglutaconic aciduria type 3, is related to optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy and optic atrophy 3, autosomal dominant, and has symptoms including ataxia, nystagmus and intellectual disability. An important gene associated with 3-Methylglutaconic Aciduria, Type Iii is OPA3 (OPA3, Outer Mitochondrial Membrane Lipid Metabolism Regulator), and among its related pathways/superpathways is Mitochondrial protein import. Affiliated tissues include eye and brain.

OMIM : 53 Type III 3-methylglutaconic aciduria is a neuroophthalmologic syndrome consisting of early-onset bilateral optic atrophy and later-onset spasticity, extrapyramidal dysfunction, and cognitive deficit. Urinary excretion of 3-methylglutaconic acid and of 3-methylglutaric acid is increased (Anikster et al., 2001). The phenotype is similar to Behr syndrome (210000) and may in some cases represent the same disorder (Sheffer et al., 1992; Lerman-Sagie, 1995). (258501)

UniProtKB/Swiss-Prot : 71 3-methylglutaconic aciduria 3: A metabolic disorder that causes a neuro-ophthalmologic syndrome consisting of early-onset bilateral optic atrophy, spasticity, extrapyramidal dysfunction and cognitive deficit. Urinary excretion of 3-methylglutaconic acid and 3-methylglutaric acid is increased. MGA3 can be distinguished from MGA1 by the absence of increase of 3- hydroxyisovaleric acid levels.

Disease Ontology : 12 A 3-methylglutaconic aciduria that has material basis in mutation in the OPA3 gene.

Wikipedia : 72 Optic neuropathy refers to damage to the optic nerve due to any cause. Damage and death of these nerve... more...

GeneReviews: NBK1473

Related Diseases for 3-Methylglutaconic Aciduria, Type Iii

Diseases in the 3-Methylglutaconic Aciduria family:

3-Methylglutaconic Aciduria, Type I 3-Methylglutaconic Aciduria, Type Iv
3-Methylglutaconic Aciduria, Type Iii 3-Methylglutaconic Aciduria, Type V
3-Methylglutaconic Aciduria, Type Viii 3-Methylglutaconic Aciduria, Type Ix

Diseases related to 3-Methylglutaconic Aciduria, Type Iii via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 23)
# Related Disease Score Top Affiliating Genes
1 optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy 33.7 OPA1 PMPCA
2 optic atrophy 3, autosomal dominant 32.6 OPA3 PMPCA
3 behr syndrome 32.6 OPA1 OPA3
4 optic atrophy 1 32.4 MFN2 OPA1 OPA6
5 3-methylglutaconic aciduria 31.1 AUH DNAJC19 OPA3 SERAC1 TMEM70
6 autosomal dominant optic atrophy plus syndrome 12.5
7 glaucomatous atrophy of optic disc 12.2
8 leber hereditary optic neuropathy 11.2
9 leber optic atrophy 11.0
10 neuropathy, hereditary motor and sensory, type via 11.0
11 leber congenital amaurosis 11.0
12 spastic paraplegia 7, autosomal recessive 10.5 MFN2 OPA1 SPG7
13 cranial nerve disease 10.5 MFN2 MT-ND4 OPA3 WFS1
14 3-methylglutaconic aciduria, type i 10.5 AUH DNAJC19 OPA3 TMEM70
15 organic acidemia 10.5 BTD SERAC1 TMEM70
16 3-methylglutaconic aciduria with deafness, encephalopathy, and leigh-like syndrome 10.5 AUH DNAJC19 OPA3 SERAC1 TMEM70
17 3-methylglutaconic aciduria, type iv 10.4 AUH DNAJC19 OPA3 SERAC1 TMEM70
18 optic nerve disease 10.4 BTD MFN2 MT-ND4 OPA1 OPA3 WFS1
19 mitochondrial metabolism disease 10.4 MT-ND4 OPA1 SERAC1 SPG7 TIMM8A
20 mitochondrial disorders 10.4 MT-ND4 OPA1 SPG7 TIMM8A
21 3-methylglutaconic aciduria, type v 10.4 AUH DNAJC19 MT-ND4 OPA3 SERAC1 TMEM70
22 scotoma 10.4 MT-ND4 OPA1
23 cortical blindness 10.2 MT-ND4 TIMM8A

Graphical network of the top 20 diseases related to 3-Methylglutaconic Aciduria, Type Iii:



Diseases related to 3-Methylglutaconic Aciduria, Type Iii

Symptoms & Phenotypes for 3-Methylglutaconic Aciduria, Type Iii

Symptoms via clinical synopsis from OMIM:

53
Neurologic Central Nervous System:
ataxia
spasticity
dysarthria
hyperreflexia
extrapyramidal signs
more
Laboratory Abnormalities:
increased urinary 3-methylglutaconic acid

Head And Neck Eyes:
optic atrophy
decreased visual acuity


Clinical features from OMIM:

258501

Human phenotypes related to 3-Methylglutaconic Aciduria, Type Iii:

55 31 (show all 17)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 55 31 frequent (33%) Frequent (79-30%) HP:0001251
2 nystagmus 55 31 frequent (33%) Frequent (79-30%) HP:0000639
3 intellectual disability 55 31 frequent (33%) Frequent (79-30%) HP:0001249
4 dysarthria 55 31 frequent (33%) Frequent (79-30%) HP:0001260
5 gait disturbance 55 31 occasional (7.5%) Occasional (29-5%) HP:0001288
6 visual impairment 55 31 hallmark (90%) Very frequent (99-80%) HP:0000505
7 choreoathetosis 55 31 hallmark (90%) Very frequent (99-80%) HP:0001266
8 spastic paraparesis 55 31 frequent (33%) Frequent (79-30%) HP:0002313
9 3-methylglutaconic aciduria 55 31 hallmark (90%) Very frequent (99-80%) HP:0003535
10 abnormality of extrapyramidal motor function 31 HP:0002071
11 spasticity 31 HP:0001257
12 hyperreflexia 31 HP:0001347
13 chorea 31 HP:0002072
14 optic atrophy 31 HP:0000648
15 cognitive impairment 31 HP:0100543
16 babinski sign 31 HP:0003487
17 reduced visual acuity 31 HP:0007663

UMLS symptoms related to 3-Methylglutaconic Aciduria, Type Iii:


abnormality of extrapyramidal motor function, muscle spasticity, ataxia

Drugs & Therapeutics for 3-Methylglutaconic Aciduria, Type Iii

Search Clinical Trials , NIH Clinical Center for 3-Methylglutaconic Aciduria, Type Iii

Cochrane evidence based reviews: optic atrophy

Genetic Tests for 3-Methylglutaconic Aciduria, Type Iii

Genetic tests related to 3-Methylglutaconic Aciduria, Type Iii:

# Genetic test Affiliating Genes
1 Optic Atrophy 28
2 3-Methylglutaconic Aciduria Type 3 28 OPA3

Anatomical Context for 3-Methylglutaconic Aciduria, Type Iii

MalaCards organs/tissues related to 3-Methylglutaconic Aciduria, Type Iii:

38
Eye, Brain

Publications for 3-Methylglutaconic Aciduria, Type Iii

Articles related to 3-Methylglutaconic Aciduria, Type Iii:

# Title Authors Year
1
The neuropsychological profile of patients with 3-methylglutaconic aciduria type III, Costeff syndrome. ( 25657044 )
2015
2
OPA3, mutated in 3-methylglutaconic aciduria type III, encodes two transcripts targeted primarily to mitochondria. ( 20350831 )
2010
3
3-Methylglutaconic aciduria type III in a non-Iraqi-Jewish kindred: clinical and molecular findings. ( 12126933 )
2002
4
Ineffectiveness of oral coenzyme Q10 supplementation in 3-methylglutaconic aciduria, type 3. ( 9533558 )
1998
5
Iraqi-Jewish kindreds with optic atrophy plus (3-methylglutaconic aciduria type 3) demonstrate linkage disequilibrium with the CTG repeat in the 3' untranslated region of the myotonic dystrophy protein kinase gene. ( 9097959 )
1997
6
3-Methylglutaconic aciduria, type 3. ( 7573769 )
1995

Variations for 3-Methylglutaconic Aciduria, Type Iii

ClinVar genetic disease variations for 3-Methylglutaconic Aciduria, Type Iii:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 OPA3 NM_025136.3(OPA3): c.415C> T (p.Gln139Ter) single nucleotide variant Pathogenic rs28937899 GRCh37 Chromosome 19, 46056897: 46056897
2 ISCA2 NM_194279.3(ISCA2): c.229G> A (p.Gly77Ser) single nucleotide variant Pathogenic/Likely pathogenic rs730882246 GRCh38 Chromosome 14, 74494329: 74494329
3 OPA3 NM_025136.3(OPA3): c.143-1G> C single nucleotide variant Pathogenic rs80356523 GRCh37 Chromosome 19, 46057170: 46057170
4 OPA3 NM_025136.3(OPA3): c.320_337del18 (p.Gln108_Glu113del) deletion Pathogenic rs80356526 GRCh37 Chromosome 19, 46056975: 46056992
5 PMPCA NM_015160.2(PMPCA): c.1066G> A (p.Gly356Ser) single nucleotide variant Pathogenic rs768643552 GRCh37 Chromosome 9, 139313082: 139313082
6 PMPCA NM_015160.2(PMPCA): c.1129G> A (p.Ala377Thr) single nucleotide variant Pathogenic rs753611141 GRCh38 Chromosome 9, 136418847: 136418847
7 OPA3 NM_025136.3(OPA3): c.539A> G (p.Ter180Trp) single nucleotide variant Likely pathogenic rs1057516497 GRCh37 Chromosome 19, 46056773: 46056773

Copy number variations for 3-Methylglutaconic Aciduria, Type Iii from CNVD:

7
# CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 173060 3 189400000 193800000 Deletion OPA1 Optic atrophy

Expression for 3-Methylglutaconic Aciduria, Type Iii

Search GEO for disease gene expression data for 3-Methylglutaconic Aciduria, Type Iii.

Pathways for 3-Methylglutaconic Aciduria, Type Iii

Pathways related to 3-Methylglutaconic Aciduria, Type Iii according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.59 DNAJC19 PMPCA TIMM8A

GO Terms for 3-Methylglutaconic Aciduria, Type Iii

Cellular components related to 3-Methylglutaconic Aciduria, Type Iii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial inner membrane GO:0005743 9.56 C19orf70 DNAJC19 MT-ND4 OPA1 PMPCA SPG7
2 mitochondrion GO:0005739 9.4 AUH C19orf70 DNAJC19 MFN2 MT-ND4 OPA1

Biological processes related to 3-Methylglutaconic Aciduria, Type Iii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein targeting to mitochondrion GO:0006626 9.37 DNAJC19 MFN2
2 mitochondrial calcium ion transmembrane transport GO:0006851 9.32 PMPCA SPG7
3 mitochondrion morphogenesis GO:0070584 9.26 OPA1 OPA3
4 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway GO:1902236 9.16 OPA1 WFS1
5 mitochondrial fusion GO:0008053 8.96 MFN2 OPA1
6 visual perception GO:0007601 8.92 DNAJC19 OPA1 OPA3 WFS1

Sources for 3-Methylglutaconic Aciduria, Type Iii

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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